In 1968, he and Joan Stuart appeared as "Giles" and "Penelope" in Les Anglaises, a recurring segment about a French-Canadian man with an English-Canadian wife, on the CBC Radio comedy series, Funny You Should Say That.

Cullen played a French-Canadian astronaut character named Commander Bi Bi Latuque alongside Ted Zeigler for the 1969 children's show, The Buddies on CFCF-TV in Montreal.[4] He honed his voice skills by working as a radio announcer, notably in his home town of Montreal on (then) MOR station CKGM doing the overnight and weekend swing shifts. From 1967-69, he was the announcer for Smothers Brothers Comedy Hour.[citation needed]

Cullen recalls auditioning for the role of the robot Optimus Prime at a casting house in Burbank, California, explaining that as he read Prime's character breakdown, he saw that it was "the opportunity of the year", and heeded his brother Larry's advice: "Peter, don't be a Hollywood hero, be a real hero. Real heroes don't yell and act tough; they are tough enough to be gentle, so control yourself."[3][5] Cullen later learned from his agent, Steve Tisherman, that he not only won the part of Prime, but also, to his surprise, the role of Ironhide as well, which he saw as a "home run".[3]

He has stated that Optimus is his favorite voice role, and that he based the voice of the Autobot leader on his older brother Larry, who served in Vietnam. "When he came home, I could see a change. He was quieter and he was a man and a hero to me," says the actor. "I watched him and listened to him. I'd never had an opportunity to do a superhero, and when that came, [that voice] just came right out of me and I sounded like Optimus."[6]

Cullen putting his handprints in wet concrete at the Optimus Prime Chinese Theatre Handprint Ceremony in September 2014

He has also stated that he had no idea of Prime's popularity until the character's controversial death in the 1986 animated film, as the studio had never given him fan letters from children addressed to Optimus. The public backlash over Optimus' death surprised producers greatly. Children were leaving the theaters because of the character's death. The writers temporarily revived the character for a single episode in Season 3 called "Dark Awakening". Initially, this was intended to be his final appearance, but after fan requests continued, "The Return of Optimus Prime", a two-part episode was produced. The original ending of "Dark Awakening" was altered in reruns to include a teaser about the return of the character.[citation needed]

Among many other television series and films, he has also lent his basso voice to many film trailers and television commercials, including announcing for the Toonami and You Are Here blocks on the Cartoon Network. Cullen spent some of his early professional years in Montreal as a radio announcer/DJ on CKGM; and as a character in a then-popular local television kids show. He acted the role of a French-Canadian astronaut, along with writer and his partner on the show, Ted Ziegler. Both Ziegler and Cullen were in the supporting cast of The Sonny & Cher Comedy Hour, as well as other network comedies of the era.